The addition of a drug commonly used to treat arthritis may reduce the risk of graft-versus-host-disease in patients who underwent haploidentical allogeneic stem cell transplant.
For many blood cancers, allogeneic hematopoietic stem cell transplant remains the only way to potentially cure the disease. However, the success of transplant relies upon how compatible the donor tissue is with the recipient’s tissue. Incompatibility can lead to a complication called graft-versus-host disease (GvHD), where the donor tissue is seen as foreign and attacked by the recipient’s body.
Addressing Donor Disparities
With some ethnic groups having smaller donor pools than others, patients receiving transplant are at an increased risk of GvHD, thus creating health disparities. Recent study results presented at the 2021 ASH Annual Conference addressed this by looking at a potential new way to treat GvHD.
“The health care disparity here stems from the fact that certain ethnic groups lack matched volunteer donors. The alternative is to use haploidentical family donors. This comes at a price of increasing the risk of GvHD. The new combination aims to decrease the risk of GvHD in haploidentical family donors. This will equalize the outcomes even when haploidentical family donors are used,” said study author Dr. Samer Al-Homsi, of the NYU Langone Perlmutter Cancer Center, in an interview with CURE®.
Currently, Black patients, Asian Americans and Hispanics are less than a third as likely than their White counterparts to find a completely matched donor, putting them at higher risk for GvHD, “the most common and feared complication of donor stem cell transplantation.”
Arthritis Drug Enters GvHD Treatment Scene
Al-Homsi and his team’s research looked at a new drug combination of cyclophosphamide, Orencia (abatacept) and tacrolimus to prevent GvHD after a haploidentical (half-match, such as one from a parent) hematopoietic stem cell transplant.
Orencia is a drug that is commonly used to treat certain forms of arthritis. When given after transplant, it blocks the activation of T cells, which play an instrumental role in GvHD.
Al-Homsi explained that in prior trials, when Orencia was added to the standard GvHD regimen of methotrexate and tacrolimus, there was a decrease in the incidence of GvHD for patients with fully matched or near-matched transplants, leading to an accelerated approval by the Food and Drug Administration (FDA) for this regimen.
Now analyzing the arthritis medication as part of a three-drug regimen to prevent GvHD in haploidentical transplant recipients, Al-Homsi is hoping to not only prevent the symptom, but also decrease the amount of time the patient has to stay on tacrolimus (which suppresses the immune system), thus speeding up recovery time as well.
“These drugs have each unique mechanisms of action that complement each other. The combination aims to target different mediators of the process of GvHD,” Al-Homsi said. “The side effects of the combination were mild and manageable. The study also decreased the duration of tacrolimus, thus reducing its unwanted side effects.”
Early Findings Show Promise
Early findings from the trial showed that among the first 23 patients with aggressive blood cancers who were given the combination over the course of three months after transplant, only four showed early signs of GvHD, and two more developed reactions weeks later. All patients were successfully treated, and there were no severe symptoms, such as liver damage of difficulty breathing.
One patient on the study died from recurrent leukemia, but the rest are cancer-free five months after transplant, with signs that the transplant is working.
The study is ongoing, and Al-Homsi said that the hope is to enroll a total of 47 patients.
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